Gold nanoparticles (GNPs) possess unique physicochemical properties that may facilitate entry into the central nervous system (CNS) where they may act therapeutically. There is little information on GNPs biodistribution in specific brain regions or extent of inflammation induction. Experiments determined the localization and neuroinflammatory response of spherical GNPs (10 nm) after IV injection in male C57Bl mice. As a supplement, a known inflammogen, lipopolysaccharide (LPS, 2 mg/kg, sc), was tested. To determine the optimal buffer concentration to maintain GNP solubility, we measured aggregation of GNPs using various PBS concentrations (10, 1, 0.1, 0.01 X). 0.01X PBS produced the least amount of GNP aggregation and was used in all studies. The next experiment verified entry of GNPs into CNS. Mice were IV injected using the tail vein (200 microg/ml 10 nm GNPs in 0.01X PBS). After 24 hrs mice were perfused transcardially with 2 % glutaraldehyde/paraformaldehyde and brains were collected. GNPs were measured using inductively coupled plasma mass spectrometry in whole brain homogenates. To specifically localize accumulation of GNPs in brain, septum, caudate, hippocampus, hypothalamus, cortex, frontal cortex, and spinal cord were dissected. Hypothalamus, hippocampus, and septum had the highest levels of GNPs (6.7, 6.2, and 4.6 microg Au/g, respectively). To evaluate brain inflammation, we used q- PCR analysis of frozen brain regions for study of pro-inflammatory mediators, LIF, CCL2 and IL1beta. GNPs did not affect cytokine/chemokine expression in cortex, frontal cortex or hippocampus. LPS, as expected, caused a marked (100-fold) increase in the same cytokines. Results show that GNPs enter brain and concentrate in specific regions without eliciting an inflammatory response. Data raise the possibility of usefulness of GNPs in drug delivery and therapeutic treatment of CNS diseases.
The Toxicologist. Society of Toxicology 52nd Annual Meeting and ToxExpo, San Antonio, Texas, March 10-14, 2013